Human organs-on-chips for disease modelling, drug development and personalized medicine

Nature Reviews Genetics, Год журнала: 2022, Номер 23(8), С. 467 - 491

Опубликована: Март 25, 2022

The failure of animal models to predict therapeutic responses in humans is a major problem that also brings into question their use for basic research. Organ-on-a-chip (organ chip) microfluidic devices lined with living cells cultured under fluid flow can recapitulate organ-level physiology and pathophysiology high fidelity. Here, I review how single multiple human organ chip systems have been used model complex diseases rare genetic disorders, study host–microbiome interactions, whole-body inter-organ reproduce clinical drugs, radiation, toxins infectious pathogens. address the challenges must be overcome chips accepted by pharmaceutical industry regulatory agencies, as well discuss recent advances field. It evident instead drug development avatars personalized medicine ever closer realization. This Review discusses types organ-on-a-chip diverse applications disease modelling, medicine, reach full potential.

Язык: Английский

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Organs-on-chips: into the next decade

Nature Reviews Drug Discovery, Год журнала: 2020, Номер 20(5), С. 345 - 361

Опубликована: Сен. 10, 2020

Язык: Английский

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A guide to the organ-on-a-chip

Nature Reviews Methods Primers, Год журнала: 2022, Номер 2(1)

Опубликована: Май 12, 2022

Organs-on-chips (OoCs) are systems containing engineered or natural miniature tissues grown inside microfluidic chips. To better mimic human physiology, the chips designed to control cell microenvironments and maintain tissue-specific functions. Combining advances in tissue engineering microfabrication, OoCs have gained interest as a next-generation experimental platform investigate pathophysiology effect of therapeutics body. There many examples there applications, making it difficult for new researchers understand what makes one OoC more suited an application than another. This Primer is intended give introduction aspects that need be considered when developing application-specific OoC. The covers guiding principles considerations design, fabricate operate OoC, well subsequent assaying techniques extract biological information from devices. Alongside this discussion current future applications technology, inform design operational decisions during implementation systems. with aim mimicking physiology range biomedical therapeutic applications. Leung, de Haan et al. report practical tips organ-on-a-chip

Язык: Английский

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Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology

Communications Medicine, Год журнала: 2022, Номер 2(1)

Опубликована: Дек. 6, 2022

Conventional preclinical models often miss drug toxicities, meaning the harm these drugs pose to humans is only realized in clinical trials or when they make it market. This has caused pharmaceutical industry waste considerable time and resources developing destined fail. Organ-on-a-Chip technology potential improve success development pipelines, as can recapitulate organ-level pathophysiology responses; however, systematic quantitative evaluations of Organ-Chips' predictive value have not yet been reported.870 Liver-Chips were analyzed determine their ability predict drug-induced liver injury by small molecules identified benchmarks Innovation Quality consortium, who published guidelines defining criteria for qualifying models. An economic analysis was also performed measure could offer if broadly adopted supporting toxicity-related decisions part workflows.Here, we show that Liver-Chip met qualification across a blinded set 27 known hepatotoxic non-toxic with sensitivity 87% specificity 100%. We this level performance generate over $3 billion annually through increased small-molecule R&D productivity.The results study how incorporating Organ-Chips into workflows substantially discovery development, allowing manufacturers bring safer, more effective medicines market less at lower costs.Drug lengthy costly, relies on laboratory fail human reactions drugs. Because this, toxic sometimes go reach once are marketplace. involves growing cells devices mimic organs body, such liver. potentially help identify toxicities earlier, but there limited research well effects compared conventional In study, 870 injury, common cause failure, found outperformed These suggest widespread acceptance decrease attrition, minimize patients, billions revenue industry.

Язык: Английский

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3D cell culture models: Drug pharmacokinetics, safety assessment, and regulatory consideration

Clinical and Translational Science, Год журнала: 2021, Номер 14(5), С. 1659 - 1680

Опубликована: Май 13, 2021

Abstract Nonclinical testing has served as a foundation for evaluating potential risks and effectiveness of investigational new drugs in humans. However, the current two‐dimensional (2D) vitro cell culture systems cannot accurately depict simulate rich environment complex processes observed vivo, whereas animal studies present significant drawbacks with inherited species‐specific differences low throughput increased demands. To improve nonclinical prediction drug safety efficacy, researchers continue to develop novel models evaluate promote use improved cell‐ organ‐based assays more accurate representation human susceptibility response. Among others, three‐dimensional (3D) physiologically relevant cellular microenvironment offer great promise assessing disposition pharmacokinetics (PKs) that influence efficacy from an early stage development. Currently, there are numerous different types 3D systems, simple spheroids complicated organoids organs‐on‐chips, single‐cell type static co‐culture equipped microfluidic flow control well hybrid combine 2D biomedical microelectromechanical systems. This article reviews application challenges PKs, safety, assessment, provides focused discussion regulatory perspectives on liver‐, intestine‐, kidney‐, neuron‐based models.

Язык: Английский

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Organs-on-chips technologies – A guide from disease models to opportunities for drug development

Biosensors and Bioelectronics, Год журнала: 2023, Номер 231, С. 115271 - 115271

Опубликована: Март 31, 2023

Current in-vitro 2D cultures and animal models present severe limitations in recapitulating human physiopathology with striking discrepancies estimating drug efficacy side effects when compared to trials. For these reasons, microphysiological systems, organ-on-chip multiorgans microdevices attracted considerable attention as novel tools for high-throughput high-content research achieve an improved understanding of diseases accelerate the development process towards more precise eventually personalized standards. This review takes form a guide on this fast-growing field, providing useful introduction major themes indications further readings. We start analyzing Organs-on-chips (OOC) technologies testing administration routes: (1) oral/rectal route by intestine-on-a-chip, (2) inhalation lung-on-a-chip, (3) transdermal skin-on-a-chip (4) intravenous through vascularization models, considering how drugs penetrate bloodstream are conveyed their targets. Then, we focus OOC (other) specific organs diseases: neurodegenerative brain blood barriers, tumor including vascularization, organoids/spheroids, engineering screening antitumor drugs, liver/kidney chips multiorgan gastrointestinal metabolic assessment biomechanical systems heart, muscles bones structures related diseases. Successively, discuss materials organ chips, microfluidic organs-on-chips, sensor integration real-time monitoring, cell lines chips. (Nano)delivery approaches therapeutics chip also described. Finally, conclude critical discussion current significance/relevance, trends, limitations, challenges future prospects terms revolutionary impact biomedical research, preclinical development.

Язык: Английский

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Towards in vitro models for reducing or replacing the use of animals in drug testing

Nature Biomedical Engineering, Год журнала: 2023, Номер 8(8), С. 930 - 935

Опубликована: Дек. 27, 2023

Язык: Английский

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Standardisation needs for organ on chip devices

Lab on a Chip, Год журнала: 2021, Номер 21(15), С. 2857 - 2868

Опубликована: Янв. 1, 2021

Standards can demonstrate technological and biological relevance, increase industry implementation support regulatory acceptance. This article will give you an overview on the state of play future needs in standardisation for OoC.

Язык: Английский

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Predictive validity in drug discovery: what it is, why it matters and how to improve it

Nature Reviews Drug Discovery, Год журнала: 2022, Номер 21(12), С. 915 - 931

Опубликована: Окт. 4, 2022

Язык: Английский

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Organ‐On‐A‐Chip Models of the Blood–Brain Barrier: Recent Advances and Future Prospects

Small, Год журнала: 2022, Номер 18(39)

Опубликована: Авг. 17, 2022

The human brain and central nervous system (CNS) present unique challenges in drug development for neurological diseases. One major obstacle is the blood-brain barrier (BBB), which hampers effective delivery of therapeutic molecules into while protecting it from blood-born neurotoxic substances maintaining CNS homeostasis. For BBB research, traditional vitro models rely upon Petri dishes or Transwell systems. However, these static lack essential microenvironmental factors such as shear stress proper cell-cell interactions. To this end, organ-on-a-chip (OoC) technology has emerged a new modeling approach to better recapitulate highly dynamic vivo microenvironment so-called neural vascular unit (NVU). Such BBB-on-a-chip have made substantial progress over last decade, concurrently there been increasing interest various diseases Alzheimer's disease Parkinson's using OoC technology. In addition, with recent advances other scientific technologies, several opportunities improve platform via multidisciplinary approaches are available. review, an overview NVU provided, applications personalized medicine discovery discussed, current future directions delineated.

Язык: Английский

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